Epidemiologic data provide evidence that only one out of three patients with juvenile-onset insulin-dependent diabetes (IDDM) develops renal complications. The pattern of appearance of diabetic nephropathy suggests that the remaining two-thirds are not susceptible. Recently we obtained preliminary data which showed an association between the risk of diabetic nephropathy and genetic predisposition to hypertension. That predisposition might also represent the basis for "susceptibility" to nephropathy in IDDM. This research proposes to investigate the association further and has the following specific aims: 1. To determine whether the risk of diabetic nephropathy is associated with parental hypertension. 2. To determine whether the risk of diabetic nephropathy is associated with a high Vmax for Na-Li countertransport in red blood cells and whether this risk is independent of the risk conferred by the presence of hypertension in parents. 3. To determine whether the risk of diabetic nephropathy is associated with the Vmax of Na, K-ATPase in red blood cells. 4. To determine whether the risk factors postulated above have a major role in the development of microalbuminuria, in the progression of it to overt proteinuria, or in both. 5. The findings will provide a basis for developing preventive programs against the development of renal complications in IDDM.